肝内胆管癌的新辅助治疗进展与临床应用综述
Neoadjuvant Therapy in Intrahepatic Cholangiocarcinoma: A Review of Recent Advances and Clinical Applications
DOI: 10.12677/acm.2026.1641451, PDF,   
作者: 焦 辉, 周鹏鹏：延安大学延安医学院，陕西 延安；张 乐：延安大学数学与计算机科学学院，陕西 延安
关键词: 肝内胆管癌；新辅助治疗；化疗；靶向治疗；免疫治疗；Intrahepatic Cholangiocarcinoma； Neoadjuvant Therapy； Chemotherapy； Targeted Therapy； Immunotherapy
摘要: 肝内胆管癌作为继肝细胞癌之后的第二大原发性肝癌，因其发病率逐年上升、且早期缺乏特异性症状，导致多数患者确诊时已处于晚期，失去了手术根治的最佳时机。当前，手术切除仍是ICC患者获得长期生存的唯一有效途径，但晚期患者的手术切除率较低，亟需有效的术前综合治疗策略。新辅助治疗作为降低肿瘤负荷、评估肿瘤生物学特性及提高手术切除率的重要手段，近年来在ICC治疗领域逐渐受到重视。本文系统综述了ICC新辅助治疗的多种方法，包括化疗、放疗、靶向治疗、免疫治疗及介入治疗，重点分析了这些策略在肿瘤降期、手术转化率及患者生存预后中的作用及临床应用价值。同时，探讨了患者筛选标准及现存挑战，展望了未来研究方向，以期为临床决策和转化医学研究提供理论支持和实践指导。
Abstract: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer after hepatocellular carcinoma. Due to its rising incidence and the lack of specific early symptoms, most patients are diagnosed at an advanced stage, having missed the optimal window for curative surgery. Currently, surgical resection remains the only effective means for ICC patients to achieve long-term survival; however, the resection rate among advanced-stage patients is low, creating an urgent need for effective comprehensive preoperative treatment strategies. Neoadjuvant therapy, as a key approach to reducing tumor burden, assessing tumor biological characteristics, and improving resection rates, has gradually gained prominence in the field of ICC treatment in recent years. This article provides a systematic review of various neoadjuvant treatment methods for ICC, including chemotherapy, radiotherapy, targeted therapy, immunotherapy, and interventional therapy, with a focus on analyzing the role and clinical value of these strategies in tumor downstaging, surgical conversion rates, and patient survival outcomes. Additionally, this review discusses patient selection criteria and existing challenges, and outlines future research directions, with the aim of providing theoretical support and practical guidance for clinical decision-making and translational medical research.
文章引用：焦辉, 周鹏鹏, 张乐. 肝内胆管癌的新辅助治疗进展与临床应用综述[J]. 临床医学进展, 2026, 16(4): 2061-2069. https://doi.org/10.12677/acm.2026.1641451

参考文献

[1] Yang, J., Wang, X. and Wu, B. (2023) Incidence Trend and Prognosis of Intrahepatic Cholangiocarcinoma: A Study Based on the SEER Database. Translational Cancer Research, 12, 3007-3015. [Google Scholar] [CrossRef] [PubMed]
[2] Jensen, M.D., West, J., Weber, B., Mortensen, F.V. and Jepsen, P. (2025) Cholangiocarcinoma in Denmark: Time-Trends in Incidence and Mortality. JHEP Reports, 7, Article ID: 101493. [Google Scholar] [CrossRef] [PubMed]
[3] Nwankwo, E.C., Guta, A., Cao, S.S., Yang, J.D., Abdalla, A., Taha, W., et al. (2024) Incidence and Long-Term Outcomes of Biliary Tract Cancers in Olmsted County, Minnesota from 1976 to 2018. Cancers, 16, Article 2720. [Google Scholar] [CrossRef] [PubMed]
[4] Suzuki, Y., Mori, T., Momose, H., Matsuki, R., Kogure, M., Abe, N., et al. (2022) Predictive Factors for Subsequent Intrahepatic Cholangiocarcinoma Associated with Hepatolithiasis: Japanese National Cohort Study for 18 Years. Journal of Gastroenterology, 57, 387-395. [Google Scholar] [CrossRef] [PubMed]
[5] Stüben, B.O., Ahmadi, S., Saner, F.H., Li, J., Neuhaus, J.P., Treckmann, J.W., et al. (2024) The Significance of Resection Margins on R0 Results in Intrahepatic Cholangiocarcinoma. Surgical Oncology, 53, Article ID: 102058. [Google Scholar] [CrossRef] [PubMed]
[6] Istanbouli, A., Patel, S., Almerey, T., Li, Z. and Stauffer, J.A. (2023) Surgical Treatment for Intrahepatic, Peri-Hilar, and Distal Cholangiocarcinoma: 20-Single Institutional Year Experience. The American Surgeon™, 89, 621-631. [Google Scholar] [CrossRef] [PubMed]
[7] Li, Q., Chen, C., Zhang, D., et al. (2025) Comparative Study of Clinicopathological Features and Prognosis of Biliary Tract Cancer in Different Locations. Chinese Journal of Surgery, 63, 963-970.
[8] Öztürk, N.B. and Jamil, L.H. (2024) An Assessment of Risk Factors for Recurrence and Survival for Patients Undergoing Liver Resection for Intrahepatic Cholangiocarcinoma. European Journal of Gastroenterology & Hepatology, 36, 766-774. [Google Scholar] [CrossRef] [PubMed]
[9] Chen, X., Du, J., Huang, J., Zeng, Y. and Yuan, K. (2022) Neoadjuvant and Adjuvant Therapy in Intrahepatic Cholangiocarcinoma. Journal of Clinical and Translational Hepatology, 10, 553-563. [Google Scholar] [CrossRef] [PubMed]
[10] Huang, J., Bai, X., Qiu, Y. and He, X. (2024) Application of AI on Cholangiocarcinoma. Frontiers in Oncology, 14, Article 1324222. [Google Scholar] [CrossRef] [PubMed]
[11] Maithel, S.K., Keilson, J.M., Cao, H.S.T., Rupji, M., Mahipal, A., Lin, B.S., et al. (2023) NEO-GAP: A Single-Arm, Phase II Feasibility Trial of Neoadjuvant Gemcitabine, Cisplatin, and Nab-Paclitaxel for Resectable, High-Risk Intrahepatic Cholangiocarcinoma. Annals of Surgical Oncology, 30, 6558-6566. [Google Scholar] [CrossRef] [PubMed]
[12] Sarwar, A., Ali, A., Ljuboja, D., Weinstein, J.L., Shenoy-Bhangle, A.S., Nasser, I.A., et al. (2021) Neoadjuvant Yttrium-90 Transarterial Radioembolization with Resin Microspheres Prescribed Using the Medical Internal Radiation Dose Model for Intrahepatic Cholangiocarcinoma. Journal of Vascular and Interventional Radiology, 32, 1560-1568. [Google Scholar] [CrossRef] [PubMed]
[13] Deng, Q., He, M., Zhang, L. and Wu, Y. (2025) Neoadjuvant Immunotherapy for Resectable Primary Liver Cancer (Review). Oncology Letters, 30, 1-16. [Google Scholar] [CrossRef] [PubMed]
[14] Xie, P., Guo, L., Zhang, B., Xu, Y., Song, Q., Shi, H., et al. (2022) Case Report: Immunotherapy Successfully Treated Brain Metastasis in Intrahepatic Cholangiocarcinoma and Literature Review. Frontiers in Oncology, 12, Article 911202. [Google Scholar] [CrossRef] [PubMed]
[15] Zou, Y., Zhu, K., Pang, Y., Han, J., Zhang, X., Jiang, Z., et al. (2023) Molecular Detection of FGFR2 Rearrangements in Resected Intrahepatic Cholangiocarcinomas: FISH Could Be an Ideal Method in Patients with Histological Small Duct Subtype. Journal of Clinical and Translational Hepatology, 11, 1355-1367. [Google Scholar] [CrossRef] [PubMed]
[16] Halder, R., Amaraneni, A. and Shroff, R.T. (2022) Cholangiocarcinoma: A Review of the Literature and Future Directions in Therapy. Hepatobiliary Surgery and Nutrition, 11, 555-566. [Google Scholar] [CrossRef] [PubMed]
[17] Chakraborty, M.A., Kumar, R., Ecker, B.L., In, H., Langan, R.C., Eskander, M., et al. (2025) Role of Radiation Therapy for Biliary Tract Cancers. Current Oncology, 32, Article 545. [Google Scholar] [CrossRef] 
[18] Wheless, M., Agarwal, R., Goff, L., Lockney, N., Padmanabhan, C. and Heumann, T. (2024) Current Standards, Multidisciplinary Approaches, and Future Directions in the Management of Extrahepatic Cholangiocarcinoma. Current Treatment Options in Oncology, 25, 127-160. [Google Scholar] [CrossRef] [PubMed]
[19] Van Treeck, B.J., Olave, M.C., Watkins, R.D., Lu, H., Moreira, R.K., Mounajjed, T., et al. (2024) Neoadjuvant Therapy Leads to Objective Response in Intrahepatic Cholangiocarcinoma. HPB, 26, 938-948. [Google Scholar] [CrossRef] [PubMed]
[20] Morita, Y., Oda, K., Matsumoto, A., Ida, S., Kitajima, R., Furuhashi, S., et al. (2025) Intrahepatic Cholangiocarcinoma with BRCA Mutation Achieved Pathological Complete Response after Neoadjuvant Gemcitabine, Cisplatin, and S-1 Therapy: A Case Report. Surgical Case Reports, 11, Article ID: cr.24-0042. [Google Scholar] [CrossRef] [PubMed]
[21] Rizzo, A. and Brandi, G. (2021) Neoadjuvant Therapy for Cholangiocarcinoma: A Comprehensive Literature Review. Cancer Treatment and Research Communications, 27, Article ID: 100354. [Google Scholar] [CrossRef] [PubMed]
[22] Colangelo, M., Di Martino, M., Polidoro, M.A., Forti, L., Tober, N., Gennari, A., et al. (2025) Management of Intrahepatic Cholangiocarcinoma: A Review for Clinicians. Gastroenterology Report, 13, goaf005. [Google Scholar] [CrossRef] [PubMed]
[23] Fujiwara, Y., Ioka, T., Matsui, H., et al. (2021) A Case of Intrahepatic Cholangiocarcinoma in the Elderly Patient with Curative Resection after Neoadjuvant Chemotherapy. Gan to Kagaku ryoho. Cancer & Chemotherapy, 48, 2085-2087.
[24] Ogura, N., Hoshino, M., Hayashi, T., et al. (2022) A Case of an Advanced Intrahepatic Cholangiocarcinoma Effectively Treated by Conversion Surgery after Neoadjuvant Chemotherapy of Gemcitabine, Cisplatin and S-1. Gan to Kagaku ryoho. Cancer & Chemotherapy, 49, 1665-1667.
[25] Massani, M., Bonariol, L. and Stecca, T. (2021) Hepatic Arterial Infusion Chemotherapy for Unresectable Intrahepatic Cholangiocarcinoma, a Comprehensive Review. Journal of Clinical Medicine, 10, Article 2552. [Google Scholar] [CrossRef] [PubMed]
[26] Li, H., Li, Y., Kang, W., Xi, J., Yan, Z. and Yang, Z. (2025) Hepatic Arterial Infusion Chemotherapy versus Systemic Chemotherapy in Unresectable Intrahepatic Cholangiocarcinoma: A Propensity Score-Matched Analysis of Efficacy and Safety. Quantitative Imaging in Medicine and Surgery, 15, 4387-4399. [Google Scholar] [CrossRef] [PubMed]
[27] Riby, D., Mazzotta, A.D., Bergeat, D., Verdure, L., Sulpice, L., Bourien, H., et al. (2020) Downstaging with Radioembolization or Chemotherapy for Initially Unresectable Intrahepatic Cholangiocarcinoma. Annals of Surgical Oncology, 27, 3729-3737. [Google Scholar] [CrossRef] [PubMed]
[28] Ahmed, O., Yu, Q., Patel, M., Hwang, G., Pillai, A., Liao, C., et al. (2023) Yttrium-90 Radioembolization and Concomitant Systemic Gemcitabine, Cisplatin, and Capecitabine as the First-Line Therapy for Locally Advanced Intrahepatic Cholangiocarcinoma. Journal of Vascular and Interventional Radiology, 34, 702-709. [Google Scholar] [CrossRef] [PubMed]
[29] Gupta, A.N., Gordon, A.C., Gabr, A., Kalyan, A., Kircher, S.M., Mahalingam, D., et al. (2022) Yttrium-90 Radioembolization of Unresectable Intrahepatic Cholangiocarcinoma: Long-Term Follow-Up for a 136-Patient Cohort. CardioVascular and Interventional Radiology, 45, 1117-1128. [Google Scholar] [CrossRef] [PubMed]
[30] Tian, H., He, Q. and Wan, C. (2025) Conversion Therapy Combined with ALPPS for the Treatment of Intrahepatic Cholangiocarcinoma: A Case Report. Frontiers in Oncology, 15, Article 1542955. [Google Scholar] [CrossRef] [PubMed]
[31] Storandt, M.H., Jin, Z. and Mahipal, A. (2022) Pemigatinib in Cholangiocarcinoma with a FGFR2 Rearrangement or Fusion. Expert Review of Anticancer Therapy, 22, 1265-1274. [Google Scholar] [CrossRef] [PubMed]
[32] Yu, Q., Ungchusri, E., Pillai, A., Liao, C., Baker, T., Fung, J., et al. (2024) Selective Internal Radiation Therapy Using Yttrium-90 Microspheres for Treatment of Localized and Locally Advanced Intrahepatic Cholangiocarcinoma. European Radiology, 34, 2374-2383. [Google Scholar] [CrossRef] [PubMed]
[33] Chan, S.L., Chotipanich, C., Choo, S.P., Kwang, S.W., Mo, F., Worakitsitisatorn, A., et al. (2022) Selective Internal Radiation Therapy with Yttrium-90 Resin Microspheres Followed by Gemcitabine plus Cisplatin for Unresectable Intrahepatic Cholangiocarcinoma: A Phase 2 Single-Arm Multicenter Clinical Trial. Liver Cancer, 11, 451-459. [Google Scholar] [CrossRef] [PubMed]
[34] Huang, X., Liao, Y., Liang, Z., Ma, J., Liang, B., Yang, S., et al. (2025) Yttrium-90 Selective Internal Radiation Therapy for Right Hepatic Malignancies: A Clinical Outcome Study. EJNMMI Research, 15, Article No. 113. [Google Scholar] [CrossRef] 
[35] Chen, Y., Liu, X., Huang, L., Chen, L. and Wang, B. (2023) Clinicopathological, Etiological and Molecular Characteristics of Intrahepatic Cholangiocarcinoma Subtypes Classified by Mucin Production and Immunohistochemical Features. Expert Review of Molecular Diagnostics, 23, 445-456. [Google Scholar] [CrossRef] [PubMed]
[36] Kim, Y., Song, J., Kim, N. and Sim, T. (2025) Recent Progress in Emerging Molecular Targeted Therapies for Intrahepatic Cholangiocarcinoma. RSC Medicinal Chemistry, 16, 2314-2359. [Google Scholar] [CrossRef] [PubMed]
[37] Keggenhoff, F.L., Castven, D., Becker, D., Stojkovic, S., Castven, J., Zimpel, C., et al. (2024) PARP-1 Selectively Impairs KRAS-Driven Phenotypic and Molecular Features in Intrahepatic Cholangiocarcinoma. Gut, 73, 1712-1724. [Google Scholar] [CrossRef] [PubMed]
[38] Meng, X., Lu, J., Zeng, H., Chen, Z., Guo, X., Gao, C., et al. (2023) The Clinical Implications and Molecular Features of Intrahepatic Cholangiocarcinoma with Perineural Invasion. Hepatology International, 17, 63-76. [Google Scholar] [CrossRef] [PubMed]
[39] Tsung, C., Quinn, P.L. and Ejaz, A. (2024) Management of Intrahepatic Cholangiocarcinoma: A Narrative Review. Cancers, 16, Article 739. [Google Scholar] [CrossRef] [PubMed]
[40] Li, J., Rocha, F.G. and Mayo, S.C. (2023) Past, Present, and Future Management of Localized Biliary Tract Malignancies. Surgical Oncology Clinics of North America, 32, 83-99. [Google Scholar] [CrossRef] [PubMed]

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